Acute phase protein levels in dogs with mast cell tumours and sarcomas

<p><b>Context:</b> The acute phase protein response is part of a non-specific and complex host response to inflammation. It occurs shortly after tissue injury and may be induced by a range of different causes, including infectious, inflammatory, neoplastic, traumatic or immunological disease. Although it was conventionally believed that APPs were exclusively hepatocyte derived, there is increasing evidence to support extra-hepatic generation in neoplastic and other disease states. In people, C-reactive protein (CRP) has been shown to be of value in identifying metastatic disease from primary renal tumours as well as showing promise for monitoring rejection of renal transplants. Serum CRP correlates with survival in colorectal cancer and oesophageal squamous cell carcinoma while serum amyloid A (SAA) concentrations correlate with cancer activity, stage and prognosis in gastric tumours. Recent immunohistochemical studies in people with oesophageal carcinoma suggest that tumour tissue may itself elaborate APP with a poorer survival and outcome associated with tumours elaborating higher levels of CRP. A similar association has been seen between alpha-1 acid glycoprotein (AGP) and colorectal tumours and ovarian carcinoma.</p> <p>As yet, studies regarding APP values in neoplastic conditions in dogs are limited, and many are non-specific. In veterinary patients, elevated levels of AGP have been identified in dogs with a range of tumours with localisation to liver and splenic tissue in one study. Another study found higher levels of AGP in dogs with non-specific tumours of grade III-IV based on the WHO Tumour Node Metastasis (TNM) scale and elevated serum AGP has been documented in non-specific tumour-bearing cats. Elevated CRP levels have been documented in both dogs and cats with lymphoma and serum CRP may be used as an indicator of complete remission status in dogs with multicentric lymphoma. Elevated levels of CRP, Haptoglobin (Hp) and SAA have been identified in dogs with mammary tumours, with significant increases over normal in the presence of metastatic disease, primary tumours greater than 5cm in diameter and those with ulceration.</p> <p>In this study we evaluated an APP profile using four APPs (CRP, Hp, SAA and AGP), in dogs with mast cell tumours (MCTs) and sarcomas to assess whether the APP profile would change in reflection of tumour presence; whether the extent of any change would correlate with tumour grade; and whether the changes would differ with tumour type.</p> <p><b>Approach:</b> Patients with naturally occurring MCTs and sarcomas presenting for staging and treatment were included if they met the study criteria. Criteria for inclusion were that the patient was not currently being treated with steroids, did not have a recent history of infectious or inflammatory disease other than the tumour, a definitive histological diagnosis was available and a full staging procedure was completed prior to surgery using standard oncological protocols to identify metastatic disease where present. Following surgical resection each tumour was submitted for full histological evaluation and grading to include assessment of the margins of excision. Cases were only enrolled in the study if blood sampling formed part of the clinical investigation and/or treatment, and where residual blood was available after diagnostic sampling which would otherwise have been disposed of as clinical waste. In brief, the CRP levels were determined by immunoturbidometric assay and Hp by means of haemoglobin binding capacity assay. SAA was measured with a commercial canine ELISA kit (TriDelta Development, Dublin, Ireland) and AGP was measured with a commercial radial immunodiffusion assay (J-Path Inc, Tokyo, Japan).</p> <p><b>Results:</b> All comparisons using continuous data were checked for normality and equality of variances and appropriate statistical tests were employed (student’s t test operationalised as a two-sample Welch’s test for samples of unequal sizes and variances, Mann-Whitney, Chi-square and Fishers exact tests as appropriate). In MCTs, the CRP and AGP were elevated above reference ranges, Hp showed no significant change and SAA dropped relative to the reference range. In sarcoma patients CRP, Hp and AGP were all elevated above reference ranges. None of the tumour grade differences were significant apart from SAA in sarcoma patients where values in grade 2 sarcoma were significantly higher than those in grade 1.</p> <p><b>Interpretation and notes of caution:</b> The numbers in our groups were small which compromises the validity of statistical evaluation so our results must be interpreted with caution. However some interesting relationships have emerged from the initial evaluation which suggests that APP profiles may have potential for screening in patients with neoplastic disease. For patients with MCTs, CRP and AGP levels would be expected to increase, with a concurrent drop in SAA levels. In sarcoma patients CRP, AGP and Hp can all be expected to increase. These initial results need to be evaluated in larger numbers of cases with naturally occurring disease to validate the findings, to assess whether the presence and extent of metastatic disease has a significant effect, and also to confirm whether the values alter after surgical resection of the primary tumour.</p> <p><b>Significance of findings:</b> If there are consistent and specific changes in APP profiles associated with different tumour types in dogs, as is the case with a wide range of cancers in humans, then there may be potential for APP profiles on routine blood samples to be used as indicators of disease, or where monitoring for recurrence. Whether they could also have potential for assessment of the presence of metastatic disease and prognosis as in people is unknown as yet.</p&gt

Phosphate applications affect the coumestrol level of medics

Western Australia has a million acres of medics including various cultivars of barrel medic, Medicago truncatula, and strand medic, M. littoralis. Both species contain coumestrol, a chemical thought to have caused delayed conception and reduced twinning rates among grazing ewes in New Zealand. No infertility has been reported among ewes grazing medic pastures in Western Australia, but coumestrol levels in both species have often been high enough to suggest the possibility of oestrogenic responses among sheep grazing them

The case for new academic workspaces

Executive summary: This report draws upon the combined efforts of a number of estates professionals, architects, academics, designers, and senior managers involved in the planning of new university buildings for the 21st century. Across these perspectives, all would agree – although perhaps for different reasons - that this planning is difficult and that a number of particular considerations apply in the design of academic workspaces. Despite these difficulties, they will also agree that when this planning goes well, ‘good’ buildings are truly transformational – for both the university as a whole and the people who work and study in them. The value of well-designed buildings goes far beyond their material costs, and endures long after those costs have been forgotten ..

Photo-response of the conductivity in functionalized pentacene compounds

We report the first investigation of the photo-response of the conductivity of a new class of organic semiconductors based on functionalized pentacene. These materials form high quality single crystals that exhibit a thermally activated resistivity. Unlike pure pentacene, the functionalized derivatives are readily soluble in acetone, and can be evaporated or spin-cast as thin films for potential device applications. The electrical conductivity of the single crystal materials is noticeably sensitive to ambient light changes. The purpose, therefore, of the present study, is to determine the nature of the photo-response in terms of carrier activation vs. heating effects, and also to measure the dependence of the photo-response on photon energy. We describe a new method, involving the temperature dependent photo-response, which allows an unambiguous identification of the signature of heating effects in materials with a thermally activated conductivity. We find strong evidence that the photo-response in the materials investigated is predominantly a highly localized heating mechanism. Wavelength dependent studies of the photo-response reveal resonant features and cut-offs that indicate the photon energy absorption is related to the electronic structure of the material.Comment: Preprint: 18 pages total,7 figure

Currents, Torques, and Polarization Factors in Magnetic Tunnel Junctions

Application of Bardeen's tunneling theory to magnetic tunnel junctions having a general degree of atomic disorder reveals the close relationship between magneto-conduction and voltage-driven pseudo-torque, as well as the thickness dependence of tunnel-polarization factors. Among the results: 1) The torque generally varies as sin theta at constant applied voltage. 2) Whenever polarization factors are well defined, the voltage-driven torque on each moment is uniquely proportional to the polarization factor of the other magnet. 3) At finite applied voltage, this relation predicts significant voltage-asymmetry in the torque. For one sign of voltage the torque remains substantial even when the magnetoconductance is greatly diminished. 4) A broadly defined junction model, called ideal middle, allows for atomic disorder within the magnets and F/I interface regions. In this model, the spin dependence of a state-weighting factor proportional to the sum over general state index of evaluated within the (e.g. vacuum) barrier generalizes the local state density in previous theories of the tunnel-polarization factor. 5) For small applied voltage, tunnel-polarization factors remain legitimate up to first order in the inverse thickness of the ideal middle. An algebraic formula describes the first-order corrections to polarization factors in terms of newly defined lateral auto-correllation scales.Comment: This version no. 3 is thoroughly revised for clarity. Just a few notations and equations are changed, and references completed. No change in results. 17 pages including 4 figure

Evaluation of radiography as a screening method for detection and characterisation of congenital vertebral malformations in dogs

Congenital vertebral malformations (CVM) are common in brachycephalic ‘screw-tailed’ dogs; they can be associated with neurological deficits and a genetic predisposition has been suggested. The purpose of this study was to evaluate radiography as a screening method for congenital thoracic vertebral malformations in brachycephalic ‘screw-tailed’ dogs by comparing it with CT. Forty-nine dogs that had both radiographic and CT evaluations of the thoracic vertebral column were included. Three observers retrospectively reviewed the images independently to detect CVMs. When identified, they were classified according to a previously published radiographic classification scheme. A CT consensus was then reached. All observers identified significantly more affected vertebrae when evaluating orthogonal radiographic views compared with lateral views alone; and more affected vertebrae with the CT consensus compared with orthogonal radiographic views. Given the high number of CVMs per dog, the number of dogs classified as being CVM free was not significantly different between CT and radiography. Significantly more midline closure defects were also identified with CT compared with radiography. Malformations classified as symmetrical or ventral hypoplasias on radiography were frequently classified as ventral and medial aplasias on CT images. Our results support that CT is better than radiography for the classification of CVMs and this will be important when further evidence of which are the most clinically relevant CVMs is identified. These findings are of particular importance for designing screening schemes of CVMs that could help selective breeding programmes based on phenotype and future studies

Phenotypic hypersusceptibility to multiple protease inhibitors and low replicative capacity in patients who are chronically infected with human immunodeficiency virus type 1

Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has also been described in some viruses from antiretroviral agent-naïve patients with primary HIV-1 infection in association with combinations of amino acid changes at polymorphic sites in the protease. Many of the viruses displaying increased susceptibility to protease inhibitors also had low replication capacity. In this retrospective study, we analyze the drug susceptibility phenotype and the replication capacity of virus isolates obtained at the peaks of viremia during five consecutive structured treatment interruptions in 12 chronically HIV-1-infected patients. Ten out of 12 patients had at least one sample with protease inhibitor hypersusceptibility (change ≤0.4-fold) to one or more protease inhibitor. Hypersusceptibility to different protease inhibitors was observed at variable frequency, ranging from 38% to amprenavir to 11% to nelfinavir. Pairwise comparisons between susceptibilities for the protease inhibitors showed a consistent correlation among all pairs. There was also a significant relationship between susceptibility to protease inhibitors and replication capacity in all patients. Replication capacity remained stable over the course of repetitive cycles of structured treatment interruptions. We could find no association between in vitro replication capacity and in vivo plasma viral load doubling time and CD4(+) and CD8(+) T-cell counts at each treatment interruption. Several mutations were associated with hypersusceptibility to each protease inhibitor in a univariate analysis. This study extends the association between hypersusceptibility to protease inhibitors and low replication capacity to virus isolated from chronically infected patients and highlights the complexity of determining the genetic basis of this phenomenon. The potential clinical relevance of protease inhibitor hypersusceptibility and low replication capacity to virologic response to protease inhibitor-based therapies deserves to be investigated further

Carbon Dioxide Dynamics During a Growing Season in Midwestern Cropping Systems

Daily and seasonal CO2-exchange dynamics between the boundary layer and biosphere is important to understanding Net Ecosystem Exchange of terrestrial ecosystems. Spatial and temporal variations of CO2 fluxes across midwestern cropping systems have not been well documented. This study was designed to monitor and evaluate spatial and temporal dynamics of CO2 exchange across a watershed region for typical production fields of corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] in the Midwest by quantifying the above-canopy, within-canopy, and soil components of C balance for this cropping system. An energy-balance approach using eddy covariance was utilized across different fields making year-around measurements in both corn and soybean fields to quantify the exchange of CO2 and H2O between the crop canopy and the atmospheric boundary layer. Within-canopy concentrations of CO2 and H2O vapor were measured with an eight-port CO2/H2O infrared analyzer. Soil respiration was quantified using soil chambers at various landscape positions throughout the growing season. Fluxes of CO2 and H2O vapor throughout the day were dependent on net radiation and the stage of canopy development. Diurnal variations in CO2 and H2O vapor fluxes revealed that the magnitude of the fluxes is large and the variation of the fluxes among fields was consistent throughout the season. Integration of the daily fluxes into seasonal totals showed large differences among crops and fields. Flux differences were the result of the effect of varying soil types on water-holding capacity. Seasonal integrated values were lower than estimates derived from biomass samples collected within the fields and the measurement of the C content of the biomass. Within-canopy recycling of soil CO2 may provide insight to this discrepancy. The techniques are available to quantify the CO2 and H2O vapor fluxes across different management systems and landscapes to help refine our understanding of the magnitude of the CO2 and H2O dynamics in cropping systems